In adult women polyarthraliga and arthritis are common complications associated with Rubella live virus vaccine. We have recently showed that cellular autoantigens (calreticulin and La) are necessary for RV replication and interact with cis-acting elements of RV RNA. Antibodies to autoantigen RNP complexes are commonly found in autoimmune diseases. Therefore, it is becoming increasingly important to devise new strategies for developing rubella vaccine which is free of such adverse reactions. We are constructing a RV infectious plasmid that has altered sites/regions that interact with either calreticulin or La antigens. This infectious RNA can replicate at suboptimal level and be eliminated by dilution effect after a few cycles of replication. Further such a "replication-crippled" RV vaccine can invoke immune response and not result in vaccine related adverse reactions. We will test such a vaccinefor safety and efficacy in monkeys and eventually be used in humans. Our research deals with understanding the molecular mechanism of adverse reactions associated with rubella virus. We have for the first time showed that host autoantigens are necessary for replication of live virus in the cell. Autoantigen interaction with RV RNA can result in the generating autoimmune response which could cause arthritic symptoms associated with RV vaccine. Research dealing with the development of recombinant rubella vaccine will have significant impact on our understanding of the safety of currently licensed live virus vaccines as well as advising manufacturers in the development of future viral vaccines. Outcome of this research will have added impact on the development of assays and methodologies that are useful in evaulating the purity of biologics during manufacturing process and lot release testing. It will also provide impetus in the development of streamlining regulatory policy to evaluate manufacturing process for recombinant viral vaccines.